THE NATURAL HISTORY OF OSTEOPENIA IN GIRLS WITH RETT SYNDROME

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 摘要 假设 这项研究的目的是根据标准数据描述患有Rett综合征(RS)的女孩和妇女的骨量减少的自然病史，并确定这些个体中是否存在骨脱矿化与饮食、内分泌或身体因素之间的关联。我们假设：1)RS女孩早期严重的骨矿含量丢失持续到成年；2)RS女孩和妇女BMC减少与步行能力下降和骨折发生率增加有关；3)RS女孩和妇女骨矿含量减少与饮食或内分泌因素关系不大。 具体目标 这项研究的具体目标包括： 1)确定RS女孩和妇女的局部和整体骨矿含量(BMC)，以绝对值和z分数的方式测量，在整个童年和成年期间，RS女孩和妇女是否显著低于健康人，后者基于年龄、性别和种族特定的标准数据； 2)确定RS女孩和妇女的BMC缺陷，以z分数衡量，是否与：a)根据既往病史/x光记录的骨折临床病史，b)基于她们的行走评分的行走能力减弱，以及c)特定的mecp2突变的存在呈正相关。 3)确定BMC的缺陷是否与下列饮食或内分泌因素呈正相关： 减少膳食钙(Ca)和维生素D的摄入量，通过饮食回忆来衡量 抗惊厥药物的使用，由临床病史决定，并由血清药物水平确认 由临床病史决定的避孕药/注射剂的使用 使用标准人体测量技术从体围和皮褶测量得出的局部肌肉(手臂、大腿、小腿)质量减少 降低血钙、磷(P)、离子钙、骨特异性碱性磷酸酶、[25-OH]维生素D、[1，25-(OH)2]维生素D、骨钙素、瘦素；或增加完整甲状旁腺素、D-端肽、尿钙/肌酐排出量

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. ABSTRACT HYPOTHESIS The purpose of this study is to characterize the natural history of osteopenia in girls and women with Rett Syndrome (RS) relative to normative data and to determine if associations between bone demineralization and dietary, endocrine, or physical factors are present in these individuals. We hypothesize that: 1) the early profound losses of bone mineral content in RS girls persist into adulthood, 2) the reduction in BMC is associated with decreased ambulatory ability and increased fracture rate in RS girls and women, and 3) their reduced bone mineral content bears little relationship with dietary or endocrine factors. SPECIFIC AIMS The specific aims of this study include: 1) To determine if regional and total body bone mineral content (BMC), measured in terms of absolute values and z-scores, by dual-energy x-ray absorptiometry (DXA) is significantly lower throughout childhood and adulthood in RS girls and women than in healthy individuals, the latter based on age-, gender-, and race-specific normative data; 2) To determine if the deficits in BMC, measured as z-scores, of RS girls and women are associated positively with: a) a clinical history of bone fractures, based on previous history/x-ray documentation, b) diminished ambulatory ability, based on their ambulation score; and c) the presence of specific MECP2 mutations 3) To determine if the deficits in BMC, measured as z-scores, are associated positively with the following dietary or endocrine factors: + Reduced dietary calcium (Ca) and vitamin D intakes, measured by dietary recall + The use of anticonvulsants, determined by clinical history and confirmed by serum drug levels + The use of birth control pills/injections, as determined by clinical history + Reduced regional muscle (arm, thigh, calf) mass derived from body circumference and skinfold measurements using standard anthropometric techniques + Decreased serum Ca, phosphorus (P), ionized Ca, bone-specific alkaline phosphatase, [25-OH]vitamin D, [1,25-(OH)2]vitamin D, osteocalcin, leptin; or increased intact PTH, D-teleopeptide, urinary Ca/creatinine output